tbuckley/cabot-search huggingface dataset:
Application of IPSET-thrombosis in 1366 Patients Prospectively Followed From the Spanish Registry of Essential Thrombocythemia
Authors: Alberto Alvarez-Larrán, Beatriz Cuevas, Patricia Velez, Soledad Noya, Gonzalo Caballero-Navarro, Francisca Ferrer-Marín, Sara Carbonell, Manuel Pérez-Encinas, María Teresa Gómez-Casares, Raúl Pérez-López, Elena Magro, Ana Moretó, Irene Pastor-Galán, Anna Angona, María Isabel Mata-Vázquez, Lucía Guerrero-Fernández, José María Guerra, Gonzalo Carreño-Tarragona, Laura Fox, Ilda Murillo, Valentín García-Gutiérrez, Elvira Mora, Ruth Stuckey, Eduardo Arellano-Rodrigo, Juan Carlos Hernández-Boluda, Arturo Pereira
Journal: HemaSphere (2023)

The International Prognostic Score of thrombosis in Essential Thrombocythemia (IPSET-thrombosis) and its revised version have been proposed to guide thrombosis prevention strategies. We evaluated both classifications to prognosticate thrombosis in 1366 contemporary essential thrombocythemia (ET) patients prospectively followed from the Spanish Registry of ET. The cumulative incidence of thrombosis at 10 years, taking death as a competing risk, was 11.4%. The risk of thrombosis was significantly higher in the high-risk IPSET-thrombosis and high-risk revised IPSET-thrombosis, but no differences were observed among the lower risk categories. Patients allocated in high-risk IPSET-thrombosis (subdistribution hazard ratios [SHR], 3.7 [95% confidence interval, CI, 1.6-8.7]) and high-risk revised IPSET-thrombosis (SHR, 3.2 [95% CI, 1.4-7.45]) showed an increased risk of arterial thrombosis, whereas both scoring systems failed to predict venous thrombosis. The incidence rate of thrombosis in intermediate risk revised IPSET-thrombosis (aged &gt;60 years, JAK2 -negative, and no history of thrombosis) was very low regardless of the treatment administered (0.9% and 0% per year with and without cytoreduction, respectively). Dynamic application of the revised IPSET-thrombosis showed a low rate of thrombosis when patients without history of prior thrombosis switched to a higher risk category after reaching 60 years of age. In conclusion, IPSET-thrombosis scores are useful for identifying patients at high risk of arterial thrombosis, whereas they fail to predict venous thrombosis. Controlled studies are needed to determine the appropriate treatment of ET patients assigned to the non-high-risk categories.
Attractive deep morphology-aware active contour network for vertebral body contour extraction with extensions to heterogeneous and semi-supervised scenarios
Authors: Shen Zhao, Jinhong Wang, Xinxin Wang, Yikang Wang, Hanying Zheng, Bin Chen, An Zeng, Fuxin Wei, Sadeer Al-Kindi, Shuo Li
Journal: Medical Image Analysis (2023)
3D Biomimetic Models to Reconstitute Tumor Microenvironment In Vitro: Spheroids, Organoids, and Tumor‐on‐a‐Chip (Adv. Healthcare Mater. 18/2023)
Authors: Wenxiu Li, Zhihang Zhou, Xiaoyu Zhou, Bee Luan Khoo, Renardi Gunawan, Y. Rebecca Chin, Liang Zhang, Changqing Yi, Xinyuan Guan, Mengsu Yang
Journal: Advanced Healthcare Materials (2023)
Peripheral blood biomarkers predict viral rebound following antiretroviral therapy discontinuation in SIV-infected, early ART-treated rhesus macaques
Authors: Malika Aid, Alessandro Colarusso, Victoria Walker-Sperling, Dan H. Barouch
Journal: Cell Reports Medicine (2023)

<h2>Summary</h2> The discovery of biomarkers that predict viral rebound after discontinuation of antiretroviral therapy (ART) would significantly contribute to the HIV cure field. We previously initiated ART in 20 rhesus macaques on days 0, 1, 2, and 3 following SIVmac251 infection. After 6 months, we discontinued ART and observed viral rebound in 9 of 20 animals, which provided an opportunity to define peripheral biomarkers on ART that predicted viral rebound following ART discontinuation. We show that interleukin-1 (IL-1), IL-6_JAK_STAT3, IL-10, transforming growth factor β (TGF-β), IL-22, and IL-23 signaling and activation of monocyte, macrophage, and antigen processing and presentation pathways during ART suppression correlated with viral rebound. These signatures were validated in a second cohort of macaques. Our data suggest that low levels of antigen and proinflammatory signaling during ART suppression correlate with the presence of a rebound-competent viral reservoir. Interventions that modulate these peripheral biomarkers may be promising candidates to evaluate as potential HIV-1 cure strategies.
Perfusable Biohybrid Designs for Bioprinted Skeletal Muscle Tissue (Adv. Healthcare Mater. 18/2023)
Authors: Miriam Filippi, Oncay Yasa, Jan Giachino, Reto Graf, Aiste Balciunaite, Lisa Stefani, Robert K. Katzschmann
Journal: Advanced Healthcare Materials (2023)

Bioactuators In article 2300151 by Robert K. Katzschmann and co-workers, a perfusable, biohybrid design enables the extrusion-based bioprinting of centimeter-scale skeletal muscle tissue that is cointegrated with synthetic anchors for tissue mechanical stimulation and crossed by longitudinal channels for passive liquid perfusion, which supports cell viability all over the tissue volume and allows for drug delivery and distribution tests.
A sweet spot for the sleeping brain: Linking human sleep physiology and glucoregulation
Authors: Niels Niethard, Manfred Hallschmid
Journal: Cell Reports Medicine (2023)

Vallat et al.1 demonstrate a positive association between the coupling of slow oscillations and sleep spindles, neurophysiological markers of NREM sleep, and next-morning glucose homeostasis. Extended findings in an independent dataset raise intriguing questions about its directionality and consistency.
A target discovery pipeline identified ILT3 as a target for immunotherapy of multiple myeloma
Authors: Francesco Di Meo, Anjushree Iyer, Keith Akama, Rujin Cheng, Christina Yu, Annamaria Cesarano, Noriyoshi Kurihara, Hirofumi Tenshin, Arafat Aljoufi, Silvia Marino, Rajesh K. Soni, Julie Roda, James Sissons, Ly P. Vu, Monica Guzman, Kun Huang, Tamara Laskowski, Hal E. Broxmeyer, David G. Roodman, Fabiana Perna
Journal: Cell Reports Medicine (2023)

Multiple myeloma (MM) is an incurable malignancy of plasma cells. To identify targets for MM immunotherapy, we develop an integrated pipeline based on mass spectrometry analysis of seven MM cell lines and RNA sequencing (RNA-seq) from 900+ patients. Starting from 4,000+ candidates, we identify the most highly expressed cell surface proteins. We annotate candidate protein expression in many healthy tissues and validate the expression of promising targets in 30+ patient samples with relapsed/refractory MM, as well as in primary healthy hematopoietic stem cells and T cells by flow cytometry. Six candidates (ILT3, SEMA4A, CCR1, LRRC8D, FCRL3, IL12RB1) and B cell maturation antigen (BCMA) present the most favorable profile in malignant and healthy cells. We develop a bispecific T cell engager targeting ILT3 that shows potent killing effects in vitro and decreased tumor burden and prolonged mice survival in vivo, suggesting therapeutic relevance. Our study uncovers MM-associated antigens that hold great promise for immune-based therapies of MM.
Plasma protein biomarkers trailblaze as early predictors of type 1 diabetes
Authors: Xiaojing Jia, Shuangyuan Wang, Jieli Lu
Journal: Cell Reports Medicine (2023)

Nakayasu et al.'s investigation1 on children from TEDDY study revealed robust predictive value of plasma protein biomarkers in identifying the emergence of persistent autoantibodies and type 1 diabetes. Remarkably, this predictive accuracy was observed six months prior to autoimmunity initiation.
Thrombocytopenic, thromboembolic and haemorrhagic events following second dose with BNT162b2 and ChAdOx1: self-controlled case series analysis of the English national sentinel cohort
Authors: Mark Joy, Utkarsh Agrawal, Xuejuan Fan, Chris Robertson, Sneha N. Anand, Jose Ordonez-Mena, Rachel Byford, Rosalind Goudie, Gavin Jamie, Debasish Kar, John Williams, Gemma L. Marsden, Victoria Tzortziou-Brown, Sir Aziz Sheikh, F.D. Richard Hobbs, Simon de Lusignan
Journal: The Lancet Regional Health - Europe (2023)

Thrombosis associated with thrombocytopenia was a matter of concern post first and second doses of BNT162b2 and ChAdOx1 COVID-19 vaccines. Therefore, it is important to investigate the risk of thrombocytopenic, thromboembolic and haemorrhagic events following a second dose of BNT162b2 and ChAdOx1 COVID-19 vaccines.We conducted a large-scale self-controlled case series analysis, using routine primary care data linked to hospital data, among 12.3 million individuals (16 years old and above) in England. We used the nationally representative Oxford-Royal College of General Practitioners (RCGP) sentinel network database with baseline and risk periods between 8th December 2020 and 11th June 2022. We included individuals who received two vaccine (primary) doses of the BNT162b2 mRNA (Pfizer-BioNTech) and two vaccine doses of ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccines in our analyses. We carried out a self-controlled case series (SCCS) analysis for each outcome using a conditional Poisson regression model with an offset for the length of risk period. We reported the incidence rate ratios (IRRs) and 95% confidence intervals (CI) of thrombocytopenic, thromboembolic (including arterial and venous events) and haemorrhagic events, in the period of 0-27 days after receiving a second dose of BNT162b2 or ChAdOx1 vaccines compared to the baseline period (14 or more days prior to first dose, 28 or more days after the second dose and the time between 28 or more days after the first and 14 or more days prior to the second dose). We adjusted for a range of potential confounders, including age, sex, comorbidities and deprivation.Between December 8, 2020 and February 11, 2022, 6,306,306 individuals were vaccinated with two doses of BNT162b2 and 6,046,785 individuals were vaccinated with two doses of ChAdOx1. Compared to the baseline, our analysis show no increased risk of venous thromboembolic events (VTE) for both BNT162b2 (IRR 0.71, 95% CI: 0.65-0.770) and ChAdOx1 (IRR 0.91, 95% CI: 0.84-0.98); and similarly there was no increased risk for cerebral venous sinus thrombosis (CVST) for both BNT162b2 (IRR 0.87, 95% CI: 0.41-1.85) and ChAdOx1 (IRR 1.73, 95% CI: 0.82-3.68). We additionally report no difference in IRR for pulmonary embolus, and deep vein thrombosis, thrombocytopenia, including idiopathic thrombocytopenic purpura (ITP), and haemorrhagic events post second dose for both BNT162b2.Reassuringly, we found no associations between increased risk of thrombocytopenic, thromboembolic and haemorrhagic events post vaccination with second dose for either of these vaccines.Data and Connectivity: COVID-19 Vaccines Pharmacovigilance study.
Bacterial clade-specific analysis identifies distinct epithelial responses in inflammatory bowel disease
Authors: Gemma L. D’Adamo, Michelle Chonwerawong, Linden J. Gearing, Vanessa R. Marcelino, Jodee A. Gould, Emily L. Rutten, Sean M. Solari, Patricia W.R. Khoo, Trevor J. Wilson, Tamblyn Thomason, Emily L. Gulliver, Paul J. Hertzog, Edward M. Giles, Samuel C. Forster
Journal: Cell Reports Medicine (2023)

Abnormal immune responses to the resident gut microbiome can drive inflammatory bowel disease (IBD). Here, we combine high-resolution, culture-based shotgun metagenomic sequencing and analysis with matched host transcriptomics across three intestinal sites (terminal ileum, cecum, rectum) from pediatric IBD (PIBD) patients (n = 58) and matched controls (n = 42) to investigate this relationship. Combining our site-specific approach with bacterial culturing, we establish a cohort-specific bacterial culture collection, comprising 6,620 isolates (170 distinct species, 32 putative novel), cultured from 286 mucosal biopsies. Phylogeny-based, clade-specific metagenomic analysis identifies key, functionally distinct Enterococcus clades associated with either IBD or health. Strain-specific in vitro validation demonstrates differences in cell cytotoxicity and inflammatory signaling in intestinal epithelial cells, consistent with the colonic mucosa-specific response measured in patients with IBD. This demonstrates the importance of strain-specific phenotypes and consideration of anatomical sites in exploring the dysregulated host-bacterial interactions in IBD.
TimiGP: Inferring cell-cell interactions and prognostic associations in the tumor immune microenvironment through gene pairs
Authors: Chenyang Li, Baoyi Zhang, Evelien Schaafsma, Alexandre Reuben, Linghua Wang, Mary Jo Turk, Jianjun Zhang, Chao Cheng
Journal: Cell Reports Medicine (2023)

Determining the prognostic association of different immune cell types in the tumor microenvironment is critical for understanding cancer biology and developing new therapeutic strategies. However, this is challenging in certain cancer types, where the abundance of different immune subsets is highly correlated. In this study, we develop a computational method named TimiGP to overcome this challenge. Based on bulk gene expression and survival data, TimiGP infers cell-cell interactions that reveal the association between immune cell relative abundance and prognosis. As demonstrated in metastatic melanoma, TimiGP prioritizes immune cells critical in prognosis based on the identified cell-cell interactions. Highly consistent results are obtained by TimiGP when applied to seven independent melanoma datasets and when different cell-type marker sets are used as inputs. Additionally, TimiGP can leverage single-cell RNA sequencing data to delineate the tumor immune microenvironment at high resolutions across a wide range of cancer types.
Obesity negatively impacts maintenance of antibody response to COVID-19 vaccines
Authors: Camille Chauvin, Sruthi Vijaya Retnakumar, Jagadeesh Bayry
Journal: Cell Reports Medicine (2023)

Severe obesity accelerates the decline of neutralizing antibodies to COVID-19 vaccines contributing to increased risk of hospitalization from breakthrough SARS-CoV-2 infections.1 These findings have repercussion on the vaccination policy for SARS-CoV-2 variants and other infectious diseases like influenza in obese population.
KEAP1/NFE2L2 Pathway Signature Outperforms KEAP1/NFE2L2 Mutation Status and Reveals Alternative Pathway-Activating Mutations in NSCLC
Authors: Christoph Arolt, Margaret Dugan, Robert Wild, Vanessa Richartz, Barbara Holz, Andreas H. Scheel, Johannes Brägelmann, Svenja Wagener-Ryczek, Sabine Merkelbach-Bruse, Juergen Wolf, Reinhard Buettner, Luigi Catanzariti, Matthias Scheffler, Axel M. Hillmer
Journal: Journal of Thoracic Oncology (2023)

Activation of the antioxidant KEAP1/NFE2L2 (NRF2) pathway leads to increased glutamine dependence and an aggressive phenotype in NSCLC. Because this pathway has been explored as a clinical target, we developed a transcriptomic signature for identifying KEAP1/NFE2L2-activated tumors.A total of 971 NSCLC samples were used to train an expression signature (K1N2-score) to predict KEAP1/NFE2L2 mutations. There were 348 in-house NSCLCs that were analyzed using a NanoString expression panel for validation.The 46-gene K1N2 score robustly predicted KEAP1/NFE2L2 mutations in the validation set irrespective of histology and mutation (area under the curve: 89.5, sensitivity: 90.2%), suggesting that approximately 90% of KEAP1/NFE2L2 mutations are pathway-activating. The K1N2-score outperformed KEAP1/NFE2L2 mutational status when predicting patient survival (score p = 0.047; mutation p = 0.215). In K1N2 score-positive but KEAP1/NFE2L2 wild-type samples, enrichment testing identified SMARCA4/BRG1 and CUL3 mutations as mimics of KEAP1/NFE2L2 mutations.The K1N2-score identified KEAP1/NFE2L2-activated NSCLC by robustly detecting KEAP1/NFE2L2mut cases and discovering alternative genomic activators. It is a potential means for selecting patients with a constitutively active KEAP1/NFE2L2 pathway.
Genome-wide association study identifies risk loci within the major histocompatibility complex region for Hunner-type interstitial cystitis
Authors: Yoshiyuki Akiyama, Kyuto Sonehara, Daichi Maeda, Hiroto Katoh, Tatsuhiko Naito, Kenichi Yamamoto, Koichi Matsuda, Yuji Yamanashi, Yoichi Furukawa, Takayuki Morisaki, Yoshinori Murakami, Yoichiro Kamatani, Kaori Muto, Akiko Nagai, Wataru Obara, Ken Yamaji, Kazuhisa Takahashi, Satoshi Asai, Yasuo Takahashi, Takao Suzuki, Nobuaki Sinozaki, Hiroki Yamaguchi, Shiro Minami, Shigeo Murayama, Kozo Yoshimori, Satoshi Nagayama, Daisuke Obata, Masahiko Higashiyama, Akihide Masumoto, Yukihiro Koretsune, Takayuki Morisaki, Shumpei Ishikawa, Tetsuo Ushiku, Haruki Kume, Yukio Homma, Yukinori Okada
Journal: Cell Reports Medicine (2023)

Hunner-type interstitial cystitis (HIC) is a rare, chronic inflammatory disease of the urinary bladder with unknown etiology and genetic background. Here, we conduct a genome-wide association study of 144 patients with HIC and 41,516 controls of Japanese ancestry. The genetic variant, rs1794275, in the major histocompatibility complex (MHC) region (chromosome 6p21.3) is associated with HIC risk (odds ratio [OR] = 2.32; p = 3.4 × 10
Multimodal immune cell phenotyping in GI biopsies reveals microbiome-related T cell modulations in human GvHD
Authors: Sebastian Jarosch, Jan Köhlen, Sakhila Ghimire, Erik Thiele Orberg, Monika Hammel, Doris Gaag, Matthias Evert, Klaus-Peter Janssen, Andreas Hiergeist, André Gessner, Daniela Weber, Elisabeth Meedt, Hendrik Poeck, Elvira D’Ippolito, Ernst Holler, Dirk H. Busch
Journal: Cell Reports Medicine (2023)

Acute graft-versus-host disease (aGvHD) is a significant complication after allogeneic hematopoietic stem cell transplantation (aHSCT), but major factors determining disease severity are not well defined yet. By combining multiplexed tissue imaging and single-cell RNA sequencing on gastrointestinal biopsies from aHSCT-treated individuals with fecal microbiome analysis, we link high microbiome diversity and the abundance of short-chain fatty acid-producing bacteria to the sustenance of suppressive regulatory T cells (Tregs). Furthermore, aGvHD severity strongly associates with the clonal expansion of mainly CD8 T cells, which we find distributed over anatomically distant regions of the gut, persistent over time, and inversely correlated with the presence of suppressive Tregs. Overall, our study highlights the pathophysiological importance of expanded CD8 T cell clones in the progression of aGvHD toward more severe clinical manifestations and strongly supports the further development of microbiome interventions as GvHD treatment via repopulation of the gut Treg niche to suppress inflammation.
A surgically optimized intraoperative poly(I:C)-releasing hydrogel prevents cancer recurrence
Authors: Francois Xavier Rwandamuriye, Cameron W. Evans, Ben Wylie, Marck Norret, Breana Vitali, Diwei Ho, Dat Nguyen, Ellise A. Roper, Tao Wang, Matt S. Hepburn, Rowan W. Sanderson, Maren Pfirrmann, Vanessa S. Fear, Catherine A. Forbes, Ken Wyatt, Anne L. Ryan, Terrance G. Johns, Marianne B. Phillips, Rupert Hodder, Connull Leslie, Brendan F. Kennedy, Rachael M. Zemek, Killugudi Swaminathan Iyer, Willem Joost Lesterhuis
Journal: Cell Reports Medicine (2023)

Recurrences frequently occur following surgical removal of primary tumors. In many cancers, adjuvant therapies have limited efficacy. Surgery provides access to the tumor microenvironment, creating an opportunity for local therapy, in particular immunotherapy, which can induce local and systemic anti-cancer effects. Here, we develop a surgically optimized biodegradable hyaluronic acid-based hydrogel for sustained intraoperative delivery of Toll-like receptor 3 agonist poly(I:C) and demonstrate that it significantly reduces tumor recurrence after surgery in multiple mouse models. Mechanistically, poly(I:C) induces a transient interferon alpha (IFNα) response, reshaping the tumor/wound microenvironment by attracting inflammatory monocytes and depleting regulatory T cells. We demonstrate that a pre-existing IFN signature predicts response to the poly(I:C) hydrogel, which sensitizes tumors to immune checkpoint therapy. The safety, immunogenicity, and surgical feasibility are confirmed in a veterinary trial in canine soft tissue tumors. The surgically optimized poly(I:C)-loaded hydrogel provides a safe and effective approach to prevent cancer recurrence.
Re: ‘Short intravenous amphotericin B followed by oral posaconazole using a simple, stratified treatment approach for diabetes or COVID-19-associated rhino-orbito-cerebral mucormycosis’ by Manesh et al.
Authors: Valliappan Muthu, Ritesh Agarwal, Arunaloke Chakrabarti
Journal: Clinical Microbiology and Infection (2023)
Hippocampal GABAergic interneurons and memory
Authors: Alexandra Tzilivaki, John J. Tukker, Nikolaus Maier, Panayiota Poirazi, Rosanna P. Sammons, Dietmar Schmitz
Journal: Neuron (2023)

One of the most captivating questions in neuroscience revolves around the brain's ability to efficiently and durably capture and store information. It must process continuous input from sensory organs while also encoding memories that can persist throughout a lifetime. What are the cellular-, subcellular-, and network-level mechanisms that underlie this remarkable capacity for long-term information storage? Furthermore, what contributions do distinct types of GABAergic interneurons make to this process? As the hippocampus plays a pivotal role in memory, our review focuses on three aspects: (1) delineation of hippocampal interneuron types and their connectivity, (2) interneuron plasticity, and (3) activity patterns of interneurons during memory-related rhythms, including the role of long-range interneurons and disinhibition. We explore how these three elements, together showcasing the remarkable diversity of inhibitory circuits, shape the processing of memories in the hippocampus.
Reconstructing language from brain signals and deconstructing adversarial thought-reading
Authors: Anne-Lise Giraud, Yaqing Su
Journal: Cell Reports Medicine (2023)

Tang et al.1 report a noninvasive brain-computer interface (BCI) that reconstructs perceived and intended continuous language from semantic brain responses. The study offers new possibilities to radically facilitate neural speech decoder applications and addresses concerns about misuse in non-medical scenarios.
Plasma metabolic fingerprints for large-scale screening and personalized risk stratification of metabolic syndrome
Authors: Yifan Chen, Wei Xu, Wei Zhang, Renyang Tong, Ancai Yuan, Zheng Li, Huiru Jiang, Liuhua Hu, Lin Huang, Yudian Xu, Ziyue Zhang, Mingze Sun, Xiaoxiang Yan, Alex F. Chen, Kun Qian, Jun Pu
Journal: Cell Reports Medicine (2023)

Direct diagnosis and accurate assessment of metabolic syndrome (MetS) allow for prompt clinical interventions. However, traditional diagnostic strategies overlook the complex heterogeneity of MetS. Here, we perform metabolomic analysis in 13,554 participants from the natural cohort and identify 26 hub plasma metabolic fingerprints (PMFs) associated with MetS and its early identification (pre-MetS). By leveraging machine-learning algorithms, we develop robust diagnostic models for pre-MetS and MetS with convincing performance through independent validation. We utilize these PMFs to assess the relative contributions of the four major MetS risk factors in the general population, ranked as follows: hyperglycemia, hypertension, dyslipidemia, and obesity. Furthermore, we devise a personalized three-dimensional plasma metabolic risk (PMR) stratification, revealing three distinct risk patterns. In summary, our study offers effective screening tools for identifying pre-MetS and MetS patients in the general community, while defining the heterogeneous risk stratification of metabolic phenotypes in real-world settings.
Hearing intervention versus health education control to reduce cognitive decline in older adults with hearing loss in the USA (ACHIEVE): a multicentre, randomised controlled trial
Authors: Frank R Lin, James R Pike, Marilyn S Albert, Michelle Arnold, Sheila Burgard, Theresa Chisolm, David Couper, Jennifer A Deal, Adele M Goman, Nancy W Glynn, Theresa Gmelin, Lisa Gravens-Mueller, Kathleen M Hayden, Alison R Huang, David Knopman, Christine M Mitchell, Thomas Mosley, James S Pankow, Nicholas S Reed, Victoria Sanchez, Jennifer A Schrack, B Gwen Windham, Josef Coresh
Journal: The Lancet (2023)